Ex Parte Srivastava et al

Patent Trial and Appeal Board

Oct 18, 2018

13974007 (P.T.A.B. Oct. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/974,007 08/22/2013
39878 7590 10/22/2018
MH2 TECHNOLOGY LAW GROUP, LLP
TIMOTHY M. HSIEH
1951 KIDWELL DRIVE
SUITE 310
TYSONS CORNER, VA 22182
FIRST NAMED INVENTOR
Shiv Srivastava
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
HMJ-112-US-Ol 1038
EXAMINER
SALMON, KATHERINE D
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
10/22/2018 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing@mh2law.com
doreen@mh2law.com
lgalvin@mh2law.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHIV SRIVASTAVA, ALBERT DOBI, TADURU SREENATH,
GYORGY PETROVICS, and CHEN SUN
Appeal2017-001981
Application 13/974,007
Technology Center 1600
Before DONALD E. ADAMS, FRANCISCO C. PRATS, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
Appellants 1 submit this appeal under 35 U.S.C. § 134 involving
claims to a method of detecting expression of ERG8 mRNA in human
prostate epithelial cells. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b ).
We REVERSE.
1 Appellants identify the Real Party in Interest as The Henry M. Jackson
Foundation For The Advancement Of Military Medicine, Inc. App. Br. 3.
Appeal2017-001981
Application 13/974,007
STATEMENT OF THE CASE
Appellants' "invention relates to ERG polynucleotide and polypeptide
sequences, as well as alterations in ERG gene expression, including splice
variants of and promoter sequences of, the ERG gene that are involved in, or
associated with, prostate cancer." Spec. ,r 3. Moreover, the Specification
explains, the "invention further relates to therapeutic compositions and to
methods of detecting, diagnosing, and treating prostate cancer." Id.
Claims 60, 61, and 63-66 are on appeal. Claim 60 is illustrative and
is reproduced below:
60. A method of detecting the expression ofEts Related Gene
8 (ERG8) mRNA in a biological sample comprising nucleic acid
isolated from human prostate epithelial cells, the method
compnsmg:
(a) combining the nucleic acid sample isolated from
human prostate epithelial cells with at least a first and a second
oligonucleotide primer under hybridizing conditions, wherein
the entire nucleotide sequence of at least one of the first or the
second oligonucleotide primers hybridizes to a region within
nucleotides 803 to 1168 of SEQ ID NO: 1 or a nucleic acid strand
complementary to said region;
(b) amplifying a plurality of amplification products when
said nucleotides 803 to 1168 of SEQ ID NO: 1 are present in the
nucleic acid sample by adding at least one polymerase activity to
the biological sample containing the first and second
oligonucleotide primers, wherein the amplification products
comprises the region within nucleotides 803 to 1168 of SEQ ID
NO: 1 to which the entire nucleotide sequence of at least one of
the first or the second oligonucleotide primers hybridizes;
( c) immobilizing the plurality of amplification products;
( d) combining an oligonucleotide probe with the
immobilized plurality of amplification products to thereby
permit the probe to hybridize to at least one immobilized
amplification product;
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Application 13/974,007
( e) detecting whether a signal results from hybridization
between the oligonucleotide probe and at least one amplification
product, and
(f) detecting expression of ERG8 mRNA in the biological
sample if the signal is detected in step ( e ), wherein the biological
sample is obtained from a subject suspected of having prostate
cancer.
App. Br. (Claims App'x i).
The claims stand rejected2 as follows:
I. Claims 60, 63, and 64 3 under 35 U.S.C. § 103(a) as obvious
over Owczarek, 4 Tomlins, 5 and Pinkel6 ("Rejection I").
II. Claims 61, 65, and 66 under 35 U.S.C. § 103(a) as obvious over
Owczarek, Tomlins, Pinkel, and Goode 7 ("Rejection II").
2 The Examiner withdrew the rejection of, now canceled, claims 46-48
under 35 U.S.C. § 101. Therefore, a rejection under§ 101 is not before us in
this appeal. Final Act. 2-8; Adv. Act. (mailed Feb. 23, 2016) 2.
3 We did not include canceled claims 62 and 67 in our deliberations. Final
Act. 10; App. Br. (Claims App'x ii-iii).
4 C.M. Owczarek et al., Detailed mapping of the ERG-ETS2 interval of
human chromosome 21 and comparison with the region of conserved
synteny on mouse chromosome 16, 324 GENE 65-77 (2004).
5 Scott A. Tomlins et al., Recurrent Fusion of TMPRSS2 and ETS
Transcription Factor Genes in Prostate Cancer, 310 SCIENCE 644--48
(2005).
6 Pinkel et al., US 5,830,645, issued Nov. 3, 1998.
7 Triona Goode et al., Nested RT-PCR, Sensitivity Controls are Essential to
Determine the Biological Significance of Detected mRNA, 193 METHODS IN
MOLECULAR BIOLOGY, VOL. 193: RT-PCRPROTOCOLS 65-79 (J. O'Connell
ed.) (2002).
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Application 13/974,007
DISCUSSION
Issue
For Rejection I, the Examiner concludes that independent claims 60
and 63 (as well as dependent claim 64) would have been obvious over
Owczarek, Tomlins, and Pinkel. Final Act. 10-13. Rejection II relies and
builds upon Rejection I, by citing Goode's teachings to address certain
limitations in dependent claims 61, 65, and 66. Id. at 13-14. On this record,
because Rejection II relies on Rejection I for establishing the obviousness of
independent claims 60 and 63 over Owczarek, Tomlins, and Pinkel, if
Rejection I fails, so does Rejection II. Accordingly, a threshold- indeed, a
dispositive - issue in this appeal is whether the Examiner established by a
preponderance of the evidence on this record that claims 60 and 63 would
have been obvious over Owczarek, Tomlins, and Pinkel.
Analysis
The Examiner finds, inter alia, that Owczarek "teaches a sequence
that encompasses the region within nucleotides 803 to 1168 of SEQ ID
No. 1." Final Act. 10. According to the Examiner, Owczarek also "teaches
that all of these alternative splice forms [ of the ERG gene] encode protein
that are transcription active and bind DNA." Id. Moreover, the Examiner
finds, Owczarek "teaches the steps of comprising [ sic, combining] a sample
with primers to amplify a target sequence that encompasses ERG8 by RT
PCR." Id.
The Examiner finds that Owczarek "does not teach using
amplification products immobilized and does not teach prostate epithelial
cells." Id. at 11. According to the Examiner, however, Pinkel teaches the
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Application 13/974,007
use of an immobilized nucleic acid sample. Id. And, the Examiner finds,
Tomlins "teaches that ETS family of genes can be detected in prostate
samples ( 646-64 7) and ... suggests that expression can be detected in
prostate epithelial cells." Id.
The Examiner concludes "it would be prima facie obvious to modify
the method of Owczarek ... to screen any sample that is known to express
the ETS family, as suggested by Tomlins et al. with the expected success of
detecting expression of ERG8." Id. The Examiner asserts that the ordinarily
skilled person "would be motivated to use any known sample form [sic] a
finite number of samples which are suggested to include the ETS family
(including ERG8)." Id. Also, the Examiner reasons, it would be obvious to
use a sample immobilization technique as taught by Pinkel. Id. at 12.
The Examiner "bears the initial burden ... of presenting a prima facie
case ofunpatentability." In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir.
1992). On this record, we are not persuaded the Examiner met the burden to
establish that claim 60 or 63 would have been obvious.
The Examiner does not provide a persuasive reason why the ordinarily
skilled person would have been motivated to perform the method as claimed.
Claim 60 (and 63) requires that the biological sample in which expression of
ERG8 mRNA is detected to have been isolated from human prostate
epithelial cells obtained from a subject suspected of having prostate cancer.
The Examiner admits, however, "that the recited prior art does not suggest a
correlation between overexpression of ERG8 and prostate cancer." Ans. 3.
Even if, as the Examiner points out (Ans. 3--4), the claims do not require
making a correlation between ERG8 expression and prostate cancer, without
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a suggestion of any correlation/relationship in the cited evidence, we are
unpersuaded the skilled person would have tested the sample type that the
claims require -prostate epithelial cells from a subject suspected of having
prostate cancer. The Examiner's assertion (Ans. 4) that "it would be
obvious to try to detect expression of any fusion gene within a known family
that has associations with the prostate" is an overstatement rooted in
hindsight. That is particularly so where, as we discuss below, the prior art
suggests that many (if not most) ERG splice forms, including the ERG8
mRNA isoform, are not generally found expressed in prostate cells.
Appellants cite evidence showing that ERG8 ( and numerous other
ERG isoforms) were not detected via PCR in human prostate cells. App. Br.
12. As Appellants point out, "Owczarek analyzed the expression of the
newly identified ERG isoforms, including ERG8, in a variety of human cell
lines, including PC3, a human prostate cancer cell line ... [and] of the 4
newly identified ERG isoforms, only ERG6 was expressed in PC3 cells."
Id. ( citing Owczarek 73, Table 2). Hence, as Appellants persuasively argue,
"Owczarek does not provide any incentive to carry out further research
regarding the role ofERG8 in prostate cancer." App. Br. 10. 8
8 According to the Examiner, Owczarek teaches that all the splice forms of
ERG are transcriptionally active and bind to DNA. Final Act. 10. We are
not persuaded that is accurate. Owczarek discloses that isoforms 1-5 are
transcriptionally active and bind DNA, but Owczarek does not extend that
disclosure to newly discovered isoforms 6-9. App. Br. 11-12; Owczarek
75, left col. Indeed, although Owczarek discloses that the new isoforms
were expressed to different extents in some cells, it teaches that "[ t ]he
significance of these isoforms [6-9] compared to the major ERG isoforms
previously identified [1-5] is unknown." Owczarek 75, left col.
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The Examiner responds that "[t]here is not secondary consideration
[evidence] provided that this specific prostate cancer cell line [in Owczarek]
would have the same expression as 'prostate epithelial cells' samples from a
subject suspected of having prostate cancer." Ans. 5. But it is the
Examiner's burden to establish a persuasive, evidence-based prima facie
case of obviousness. That burden was not met.
Contrary to the Examiner's contentions, Tomlins also fails to provide
a sufficient motivation for the skilled person to have detected expression of
ERG8 mRNA in a sample of prostate epithelial cells from a subject
suspected of having prostate cancer. Tomlins is silent regarding ERG8.
Although Tomlins teaches that certain types of £TS-transcription factor
genes, ERG and ETVJ, were identified as "outliers" in prostate cancer
(Tomlins, Abstract), Appellants provide evidence that the ERG8 isoform
materially differs from the transcription factors described in Tomlins. In
particular, Appellants point out that "ERG8 does not contain the highly
conserved 3' DNA binding domain" like ERG and ETVJ. App. Br. 11
( citing Spec. ,r 68). As Appellants explain, this highly conserved binding
region - missing in ERG8 - is necessary for the formation of the fusion
constructs with TMRPSS2, which fusion constructs are widely observed in
prostate cancer. App. Br. 12; Tomlins 644 ("We identified recurrent gene
fusions of the 5' untranslated region of TMPRSS2 to ERG or ETVJ in
prostate cancer tissues with outlier expression"). So, Appellants contend,
the evidence indicates "that this DNA binding domain, particularly when
fused to an androgen-regulated promoter from a different gene [TMPRSS2],
gives rise to aberrant gene expression and prostate cancer tumorigenesis."
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Application 13/974,007
App. Br. 12. 9 In other words, based on Tomlins, only certain £TS-related
transcription factors with the highly conserved DNA binding domain would
be expected to be indicative of, and overexpressed in, cancerous prostate
cells. The Examiner provides no persuasive response to Appellants'
arguments and evidence on these points. Based on the absence of this
seemingly significant DNA binding domain in ERG8, we are unpersuaded
on this record that the skilled artisan would have been motivated to detect
the expression of ERG8 in a sample of prostate epithelial cells of a subject
suspected of having prostate cancer.
For similar reasons, we are unpersuaded the Examiner has made a
sufficient showing that a person of ordinary skill in the art would have had a
reasonable expectation of success in carrying out the method as claimed. 10
As already discussed, ERG8 mRNA was not detected in at least one line of
9 Appellants' argument is consistent with Tomlins, which discloses that
"[ c ]ell line experiments suggest that the androgen-responsive promoter
elements of TMPRSS2 mediate the overexpression of ETS family members
in prostate cancer." Tomlins 644; see also id. at 645 (describing fusions
between a promoter region of EWSBRI and a highly conserved 3' DNA
binding region of ERG and ETVI observed in Ewing sarcoma).
10 The Examiner suggests the claims do not require detection of expression.
Ans. 5. We disagree. We recognize the word "if' in step (f) of claim 60.
But, as Appellants argue, we agree that "detecting expression of ERG8" is
actually required to practice the claims. Reply Br. 3--4 (the pages of the
Reply Brief are unnumbered but we treat as though it includes numbered
pages 1-5). This interpretation is reinforced by the preamble, which also
recites "detecting the expression of Ets Related Gene 8 (ERG8) mRNA in a
biological sample comprising nucleic acid isolated from human prostate
epithelial cells." The preamble is relied upon as providing antecedent basis
for multiple limitations of the claims and, thus, is limiting here.
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Application 13/974,007
cancerous prostate cells. Owczarek, 73 (Table 2); App. Br. 12-13. And,
because ERG8 lacks the binding domain that contributes to the formation of
fusion constructs thought to be responsible for causing overexpression of
certain £TS-related genes observed in prostate cancer, we are not persuaded
on this record that the skilled person would have expected to detect ERG8 in
prostate epithelial cells of a subject suspected of having prostate cancer.
The Examiner further failed to establish that either of Pinkel or
Goode, alone or in combination, make up for the foregoing deficiency in the
combination of Owczarek and Tomlins.
For the above reasons, we reverse the rejection of claims 60 and 63 as
obvious over Owczarek, Tomlins, and Pinkel. We also reverse the rejections
of dependent claim 64 (Rejection I) and dependent claims 61, 65, and 66
(Rejection II), which rejections rely upon the Owczarek, Tomlins, and
Pinkel combination for the obviousness rejection of independent claims 60
and 63.
SUMMARY
We reverse the rejections for obviousness on appeal.
REVERSED
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